Effect of aminophylline on post-ischemic edema and brain injury was studied in cats subjected to the middle cerebral artery (MCA) occlusion for 1 hour. Administration of aminophylline 22.8 mg/kg infused for 15 minutes at the time of release of MCA occlusion resulted in suppression of reactive hyperemia and proved to have an unequivocal beneficial effect on development of post-ischemic edema and brain injury. The animals with aminophylline showed no breakdown of the blood-brain barrier to protein tracers and showed no significant edema in the ischemic regions, when sacrificed 3 hours after release of MCA occlusion. Also, cats with aminophylline treatment revealed significantly milder ischemic injury when studied histologically at 3 and 14 day periods after recirculation. Our studies thus demonstrate a marked beneficial effect of aminophylline with a potential to be considered for treatment of patients in certain clinical conditions.